Inflammasome Activation and Regulation by Pathogenic Bacteria: Balancing Host Defense and Tissue Damage
DOI:
https://doi.org/10.37022/jcls.v9i2.233Keywords:
Inflammasome, Pathogenic Bacteria, Infection, Immune responseAbstract
The inflammasome, a cytosolic multiprotein complex, is essential to the innate immune response by detecting danger-associated signals and pathogenic microorganisms. During bacterial infections, inflammasome activation contributes to pathogen clearance and the initiation of protective immune responses by promoting the maturation of the pro-inflammatory cytokines interleukin (IL)-1 and IL-18 and triggering pyroptotic cell death. However, dysregulated or excessive inflammasome activation may lead to tissue damage, chronic inflammation, and the development of severe inflammatory disorders. This review provides a summary of the current understanding of inflammasome biology, focusing on the molecular mechanisms that govern bacterial infection-related activation and regulation. The NLRP3, NLRC4, AIM2, NLRP1, and Pyrin roles in the inflammasome, as well as the canonical and non-canonical signaling pathways, are discussed. The review also discusses the various virulence mechanisms by which major pathogenic bacteria, such as Salmonella enterica, Listeria monocytogenes, Helicobacter pylori, Mycobacterium tuberculosis, Pseudomonas aeruginosa, Shigella spp., Escherichia coli, and Staphylococcus aureus, either activate or evade inflammasome signaling. The roles of mitochondrial dysfunction, reactive oxygen species, ion fluxes, autophagy, and post-translational modifications are also examined in light of recent advancements in the regulation of inflammasome activity. Last but not least, we look at promising new treatments that target inflammasome components and downstream inflammatory mediators as ways to control excessive inflammation while maintaining strong antibacterial immunity. A comprehensive understanding of inflammasome biology will support the development of novel host-directed therapies for bacterial infectious diseases.
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